More than one hundred Cu/Zn-superoxide dismutase 1 (SOD1) genetic mutations have been characterized; these mutations lead to the death of motor neurons in amyotrophic lateral sclerosis (ALS). In its native form, the SOD1 protein is expressed as a homo-dimer in the cytosol. In vitro studies have shown that SOD1 mutations impair the dimerization kinetics of the protein, and in vivo studies have shown that SOD1 forms aggregates in patients with familial forms of ALS. In the present study, we analyzed wild type (wt) SOD1 and 9 mutant (mt) forms of the protein by non-invasive fluorescence techniques. Using microscopic techniques such as fluorescence resonance energy transfer, fluorescence complementation, images based quantification and fluorescence correlation spectroscopy, we studied SOD1 dimerization, oligomerization, and aggregation. Our results indicate that SOD1 mutations lead to an impairment in SOD1 dimerization and subsequently affect protein aggregation. We also show that SOD1 wt and mt proteins can dimerize, however aggregates are predominantly composed of SOD1 mt proteins.